The proposed study will examine the range and mode of action of substances derived from human serum which are able to suppress in vivo and in vitro immune responsiveness. We have identified several active fractions of human serum having this property and will attempt to further purify and characterize them from a physico-chemical and immunologic point of view. The means of assay include mixed lymphocyte reactivity, delayed hypersensitivity in vivo, allograft survival, antibody production and effect on non-immunologic tissues (chalone effect). An examination of possible cytotoxic action, alterations in lymphoid organs or cells on a structural level, and induced changes in incorporation of precursor substances (purines, pyrimidines, amino acids, etc.) will be conducted.